Induction of cardiac nitric oxide synthase 2 in rats exposed to chronic hypoxia

Induction of nitric oxide synthase (NOS2, also designated as (NOS) in the h eart is known to occur in response to various stimuli. It is not known, how ever, whether in vivo hypoxia leads to cardiac NOS2 induction. We thus inve stigated the effects of normobaric hypoxia (10% O-2 for 8, 15 and 21 days) on NOS2 protein expression and enzyme activity in rat right ventricle (RV) and left ventricle (LV). Chronic hypoxia induced RV hypertrophy: the RV wei ght to body weight ratio was increased by 45%, upon 15 days of exposure. wi th no change thereafter and no change in left ventricular (LV) weight. Trea tment of hypoxic rats with L-NAME for 1 month decreased pulmonary artery pr essure and RV hypertrophy compared to hypoxic non-treated rats. NOS2 activi ty detected by [H-3] L-arginine to [H-3] L-citrulline conversion increased in RV during hypoxia, with a maximum at 15 days (+ 161%, of control rats; P <0.05), whereas as it increased less (by 60%) in LV. In parallel, after 15 days of hypoxia there was a three-fold increase in NOS2 protein abundance d etected by Western blotting using an isoform-specific antibody in the RVs ( two-fold increase in the LV). Immunochemistry with the specific antibody de monstrated the expression in cardiomyocytes isolated from both ventricles o f normoxic and hypoxic rats. Protein kinase C (PKC) content and activity wa s unchanged in LV of hypoxic rats, but increased in RV: as compared with no rmoxic rats. These results clearly show that, in the heart, NOS2 is upregul ated by hypoxia with an expression in cardiomyocytes of both ventricles, In addition, NOS2 is more inducible in the right hypertrophied ventricle than in the left non-hypertrophied hypoxic ventricle, (C) 1999 Academic Press.